6. ABSTRACT Background: Psychological stress has been hypothesized to play a role in breast cancer etiology. Although this relationship has been observed in several studies, it has not been consistently demonstrated across studies. One potential reason for this discrepancy may be that individuals vary in their physiological response to stressors. Specifically, a causal association between stress and breast cancer is supported by the well- established physiological response to stressors, which involves activation of hypothalamic-pituitary-adrenal (HPA) axis and consequently increased secretion of dehydroepiandrosterone (DHEA), and its sulfate (DHEAS), hormones that are significantly elevated in postmenopausal women who develop breast cancer. Individuals' hormonal responses to stressors vary considerably due to psychosocial, behavioral, and genetic differences and an individual's response to a stressor may be more important than the stressor itself in relationship to disease. Specific Aims: Specific aims of our long-term research are to identify genetic polymorphisms and psychosocial characteristics that contribute to differences in HPA responsivity to an acute psychological stressor measured by changes in blood hormones following the Trier Social Stress Test (TSST) and determine if these polymorphisms and psychosocial characteristics are associated with breast cancer risk. In this pilot study, we will: 1) obtain expertise administering the TSST; 2) determine our ability to recruit for a study based on the TSST; 3) obtain preliminary data on differences in changes in blood levels of HPA hormones following the TSST between carriers and non-carriers of selected polymorphisms in HPA axis genes and by psychosocial and environmental factors. Design: Forty postmenopausal women not taking hormones will be recruited and the TSST will be administered following a standard protocol. Selected HPA hormones will be measured at several time points before and after administering the TSST. Hormonal response to the TSST will be compared in terms of peak hormone concentrations and area under the curve. The proposed pilot study will collect important preliminary data that could lead to identification of women at increased risk for breast cancer and use of targeted interventions that blunt the HPA axis response to stressors to potentially decrease risk of breast cancer. 7. RELEVANCE TO PUBLIC HEALTH The proposed pilot study will provide valuable preliminary data to support a larger, full-scale study to examine biological mechanisms of psychosocial effects on breast cancer risk. Information learned from our larger study could lead to identification of women at increased risk of breast cancer related to their genetic make-up or psychosocial characteristics and could suggest targets for interventions to prevent breast cancer. [unreadable] [unreadable] [unreadable]